In experimental pancreatic carcinogenesis in rats, the evidence suggests that the development of pancreatic acinar cell carcinoma passes through the stage of hyperplastic nodules. The nature of these nodular lesions in the pancreas following the administration of 4-hydroxy aminoquindine-1-oxide (4HAQO) and azaserine will be examined ultrastructurally and the cellular alterations that accompany the nodules which become invasive cancer will be characterized. Similarly, the sequence of histological alterations following the implantation of DMBA into the pancreas will be examined to determine whether the induction of cancer of the pancreas in this model system follows a sequence of cellular transformation with clearly definable preneoplastic lesions. Special emphasis will be placed on the delineation of the morphological appearence of cancer cells of acinar cell origin when they maintain and/or loose the specialized functions. Attempts will be made to grow cells of pancreatic acinar cell cancer in tissue culture or in the syngeneic rats. Morphological appearance of zymogen granules will be correlated to function of amylase synthesis. Through histopathological and ultrastructural characterizaton of well defined preneoplastic population of cells in the pancreas, it is hoped to gain further insight as to what levels of cellular organization are the major alteration of phenotypes expressed in the preneoplastic and malignant cells. BIBLIOGRAPHIC REFERENCE: Shinozuka, H., Popp, J.A. and Konishi, Y. Ultrastructure of atypical acinar cell nodules in rat pancreas induced by 4-hydroxyaminoquinaline-1-oxide. Lab. Invest. 34:501-509, 1976.